Long-term Methimazole Treatment Research Articles

Risk of recurrence at the time of withdrawal of short- or long-term methimazole therapy in patients with Graves' hyperthyroidism: a randomized trial and a risk-scoring model.

In Graves' disease, administration of low-dose methimazole for more than 60 months induces higher remission rates compared with the conventional duration of 12-18 months. However, the risk of recurrence and its predictors beyond 48 months of drug withdrawal are not known. The aims of this study were to determine the risk of recurrence during 84 months after withdrawal of short- or long-term methimazole therapy and a risk stratification for recurrence of hyperthyroidism. A total of 258 patients were treated with methimazole for a median of 18 months and randomized to discontinuation of the drug(conventional short-term group; n = 128) or continuation of the treatment up to 60-120 months(long-term group; n = 130). Patients were followed for 84 months after methimazole withdrawal. Cox proportional hazards modeling was performed to identify factors associated with relapse and develop a risk-scoring model at the time of discontinuing the treatment. Hyperthyroidism recurred in 67 of 120(56%) of conventionally-treated patients versus 20 of 118(17%) of those who received long-term methimazole treatment, p < 0.001. Age, sex, goiter grade, triiodothyronine, thyrotropin, and thyrotropin receptor antibodies were significant predictors of recurrence in both "conventional" and "long-term" groups but free thyroxine just in the "long-term" group. The risk-scoring model had a good discrimination power (optimism corrected c-index = 0.78,95%CI = 0.73-0.82) with a range of 0-14 and sensitivity of 86% and specificity of 62% at the risk-score of eight. A relapse-free state was achieved in 83% of patients with Graves' hyperthyroidism 84 months after cessation of long-term methimazole treatment which could be predicted by some significant predictors in a simple risk-scoring system.

Sustained Euthyroidism during Thionamide Antithyroid Drug Treatment: Comparison of Short- and Long-term Methimazole Therapy

Background: Extended low serum thyrotropin (TSH) levels may increase the risk of cardiovascular events in patients with hyperthyroidism. Objectives: This study aimed to compare the time spent with sustained normal TSH concentration following short- and long-term methimazole treatment. Methods: A total of 258 patients with Graves’ hyperthyroidism completed 18 - 24 months of methimazole therapy and were randomized to discontinue treatment (n = 128, short-term group) or continue an additional 36 - 102 months of methimazole therapy (n = 130, long-term group). Clinical and laboratory evaluations were performed every 6 months for 132 months after randomization. Results: There was no difference in serum-free thyroxine, triiodothyronine, and TSH concentrations between the 2 groups at the time of randomization. Of 128 patients in the short-term group, 5 left in follow-up, 2 became hypothyroid, 67 (54%) had a relapse of hyperthyroidism, and only 54 (44%) were euthyroid at the end of the study. Among 130 patients on the long-term methimazole therapy, 4 were left in follow-up, 24 developed hyperthyroidism, 4 developed hypothyroidism, and 98 (78%) were euthyroid 132 months post-randomization. Total time spent on euthyroidism was 90.4% ± 8.1% of the study period in the short-term and 95.8% ± 7.0% in the long-term treatment groups (P &lt; 0.001). The lowest time spent in euthyroidism (74.6% ± 6.4% of the study period) belonged to 29 (24%) patients in the short-term group under levothyroxine therapy because of fluctuation in serum TSH. Patients in both groups with hyperthyroidism relapse who chose methimazole therapy spent &gt;90% of the study time in euthyroidism. Conclusions: In patients with Graves' hyperthyroidism, sustained normal serum TSH levels were more common in the long term as compared to the short-term methimazole treatment.

Long-Term, Low-Dose Methimazole Therapy Is Effective in Protecting against Relapses in Graves’ Disease

Clinical ThyroidologyVol. 35, No. 02 HyperthyroidismFree AccessLong-Term, Low-Dose Methimazole Therapy Is Effective in Protecting against Relapses in Graves’ DiseaseGiuseppe BarbesinoGiuseppe BarbesinoThyroid Unit, Division of Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A.Search for more papers by this authorPublished Online:8 Feb 2023https://doi.org/10.1089/ct.2023;35.54-56AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Review of: Lertwattanarak R, Kunavisarut T, Sriussadaporn S 2022 Benefits of Long-term continuation of low-dose methimazole therapy in the prevention of recurrent hyperthyroidism in Graves' hyperthyroid patients: A randomized prospective controlled study. Int J Endocrinol 2022:1705740. PMID: 36267362.SUMMARYBackgroundThe management of Graves’ disease (GD) hyperthyroidism has been evolving over the past two decades. The traditional standard of care suggested treatment with methimazole for 12 to18 months followed by radioactive iodine (RAI) treatment or surgery (1) in patients not achieving remission, where remission is defined as the ability to maintain euthyroidism after discontinuation of methimazole. This recommendation is supported by the recognition that longer courses of antithyroid drugs do not increase the rate of lasting remissions after discontinuation (2). This strategy has become less attractive owing to increasing evidence that RAI can cause or worsen thyroid eye disease (3) on the one hand and on the other to concerns about quality of life with hypothyroidism, even when thyroid hormone is optimally replaced (4). This study (5) was conducted to understand whether long-term therapy with low-dose methimazole could protect GD patients from relapses of hyperthyroidism.MethodsThis was a randomized controlled study in adult GD patients who had been euthyroid while taking methimazole for at least 6 months prior to randomization. The patients were randomly assigned to either continue methimazole at low doses (2.5–5 mg daily) or discontinue methimazole. The subjects’ thyroid function was then monitored every 6 months for 36 months. Standard diagnostic criteria for GD were adopted for inclusion. Patients who had already experienced a relapse were excluded. The primary outcome measured was the cumulative incidence of relapsing hyperthyroidism in the two groups.ResultsNinety-two patients were randomly assigned to the discontinuation group and 92 to the low-dose treatment group. Except for minor differences, the two groups were very similar for most epidemiologic parameters (86% female vs. 84% and mean [±SD] age, 39.9±10.9 vs. 42.2±14.9 years), indicating a reliable randomization process. The average duration of methimazole therapy prior to randomization was 37 months in the discontinuation group and 32 months in the low-dose group (not statistically different). In the discontinuation group, the number of relapses increased progressively and uniformly during the study time, reaching 41.2% at 36 months. In the low-dose group, the rate of relapse was 11%, and it was reached 18 months after randomization, with no additional relapses after that time. There were no recorded side effects during the study period.ConclusionsIn patients with GD, long-term treatment with 2.5 to 5 mg of methimazole daily is safe and effective in preventing the relapse of hyperthyroidism. This strategy is a valid alternative to RAI therapy and thyroidectomy in patients who want neither and yet worry about relapses of hyperthyroidism.COMMENTARYGraves’ disease, like many other autoimmune diseases, is often characterized by flares and remissions (6). Patients taking methimazole are typically treated for 12 to 18 months, after which a discontinuation trial is performed, in the hope of a lasting remission. Measuring serum TSH receptor antibodies (TRAbs) before antithyroid drug discontinuation helps to identify patients who are at high risk for early relapses in the 3 to 6 months after discontinuation (7). However, 20 to 30% of patients negative for TRAbs will still relapse months to years after the discontinuation (8,9). This observation, and mounting diffidence towards RAI therapy and surgery, has led to increased interest for long-term methimazole treatment. The data so far available have been mostly retrospective, or have addressed only select patient groups (for example, patients who already have experienced a relapse) (10). Like other endocrinologists, I have been advising some of my patients with GD who appear to be “currently” in remission, to continue methimazole indefinitely at very low doses, typically 2.5 mg daily. This article provides good-quality evidence to support such a practice, which I will continue to apply, especially to older patients and patients who had experienced particularly intense symptoms from the hyperthyroidism at the time of its first presentation.Disclosures: The author has no relevant conflicts of interest to declare.

Treatment of post-radioactive iodine relapse of hyperthyroidism: comparison of long-term methimazole and radioactive iodine treatment.

This study aimed to compare the time to achieve euthyroidism and sustained control of hyperthyroidism after treatment with radioactive iodine (RAI) or long-term methimazole (LT-MMI) in patients with post-RAI relapsed hyperthyroidism. Sixty four patients with recurrence of hyperthyroidism after RAI treatment were randomly assigned to either RAI or LT-MMI treatment. Both groups were followed every 1-3months in the first year and then every 6months for a total of 60months. In RAI and LT-MMI groups, mean age was 49.0 ± 12.1 and 50.1 ± 14.6years and time of relapse of hyperthyroidism after previous RAI treatment was 23.2 ± 18.8 and 20.8 ± 17.1months, respectively. At the end of study, in the LT-MMI group, 31 (97%) and 1 (3%) were euthyroid and hypothyroid, respectively; in the RAI group, 8 (25%) patients were euthyroid, whereas 18 (56%), 3 (9.5%) and 3 (9.5%) had overt hypothyroidism, subclinical hypothyroidism and hyperthyroidism, respectively. Mean time to euthyroidism was 9.4 ± 5.0months in the RAI group and 3.5 ± 2.8months in the LT-MMI group (p < 0.001). Patients in the RAI group spent 77.7 ± 14.0 percent and those in the LT-MMI group spent 95.2 ± 5.9 percent of 60months in the euthyroid state (p < 0.001). In patients with post-RAI relapse of hyperthyroidism, LT-MMI treatment was superior to radioiodine because of faster achievement of euthyroidism and more sustained control of hyperthyroidism during 60months of follow-up.

Control of Graves\u2019 hyperthyroidism with very long-term methimazole treatment: a clinical trial

BackgroundLong-term antithyroid drug therapy has become one of the options for treatment of Graves’ hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years.MethodsFifty nine patients with Graves’ disease on long-term MMI for 14.2 ± 2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years.ResultsOf 27 patients who continued MMI up to 24 years, suppressed serum thyrotropin (TSH) was not observed in any patient after the seventh year of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8 ± 1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study.ConclusionsLong-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves’ hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research.Trial registrationIRCT201009224794N1, 2010-10-25. Retrospectively registered.https://www.irct.ir/trial/5143.

Long-term methimazole therapy in juvenile Graves’ disease: a randomized trial

BACKGROUND AND OBJECTIVES: Recent studies show that long-term (LT) antithyroid drugs reduce relapse of hyperthyroidism in patients with Graves’ disease. Our objective was to evaluate the effectiveness and safety of LT methimazole treatment and to compare remission rates in Graves9 disease patients after LT and short-term (ST) therapy. METHODS: In this randomized, parallel group trial, 66 consecutive patients with untreated juvenile Graves’ hyperthyroidism were enrolled. After a median 22 months of methimazole treatment, 56 patients were randomly assigned to either continue low-dose methimazole treatment (n = 24, LT group) or to discontinue treatment (n = 24, ST group). Twenty-four patients in LT group completed 96 to 120 months of methimazole treatment. Patients in both groups were managed for 48 months after discontinuation of treatment. RESULTS: Except for 3 cases of cutaneous reactions, no other adverse events were observed throughout 120 months of methimazole therapy. Serum free thyroxine, triiodothyronine, thyrotropin, and thyrotropin receptor antibody remained normal, and the required daily dosage of methimazole was gradually decreased from 5.17 ± 1.05 mg at 22 months to 3.5 ± 1.3 mg between 96 and 120 months of treatment (P CONCLUSIONS: LT methimazole treatment of 96 to 120 months is safe and effective for treatment of juvenile Graves’ disease. The four-year cure rate of hyperthyroidism with LT methimazole treatment is almost 3 times more than that of ST methimazole treatment.

Long-term Methimazole Therapy in Juvenile Graves' Disease: A Randomized Trial.

Recent studies show that long-term (LT) antithyroid drugs reduce relapse of hyperthyroidism in patients with Graves' disease. Our objective was to evaluate the effectiveness and safety of LT methimazole treatment and to compare remission rates in Graves' disease patients after LT and short-term (ST) therapy. In this randomized, parallel group trial, 66 consecutive patients with untreated juvenile Graves' hyperthyroidism were enrolled. After a median 22 months of methimazole treatment, 56 patients were randomly assigned to either continue low-dose methimazole treatment (n = 24, LT group) or to discontinue treatment (n = 24, ST group). Twenty-four patients in LT group completed 96 to 120 months of methimazole treatment. Patients in both groups were managed for 48 months after discontinuation of treatment. Except for 3 cases of cutaneous reactions, no other adverse events were observed throughout 120 months of methimazole therapy. Serum free thyroxine, triiodothyronine, thyrotropin, and thyrotropin receptor antibody remained normal, and the required daily dosage of methimazole was gradually decreased from 5.17 ± 1.05 mg at 22 months to 3.5 ± 1.3 mg between 96 and 120 months of treatment (P < .001). Hyperthyroidism was cured in 92% and 88% of LT patients and in 46% and 33% of ST patients, 1 and 4 years after methimazole withdrawal, respectively. LT methimazole treatment of 96 to 120 months is safe and effective for treatment of juvenile Graves' disease. The four-year cure rate of hyperthyroidism with LT methimazole treatment is almost 3 times more than that of ST methimazole treatment.